The present invention relates to the field of magnetic resonance liquid sample changers. More specifically, the invention relates to the narrow field of automatic magnetic resonance liquid sample changers for use with a significant number of liquid samples to be consecutively analyzed.
Magnetic resonance spectroscopy is an aspect of analytical chemistry which includes Nuclear Magnetic Resonance (NMR) spectroscopy. This technique is used to determine the characteristics of a particular sample and to identify basic structures and compositions of that sample based on a resulting spectrum. In some industrial and educational applications it has often been desirable to prepare a large number of similar samples for NMR analysis. After preparation of these samples each needs to be entered individually into an analysis chamber, analyzed and removed from the chamber. The aforementioned procedure may be performed either manually, in which case the operator, loads and unloads the samples by hand, or automatically, using an apparatus such as the one shown in European Patent Number 0197791 A2 to Smallcombe and Codrington. The former method is obviously costly and time consuming for the operator while the latter, although not necessarily quicker, frees up the operator to tend to other matters. In some instances the automatic sample changing system may run completely independent after initial activation, allowing samples to be analyzed overnight or over the weekend at minimal cost. It would seem that these reasons have led those skilled in the art to view the field of automatic magnetic resonance sample changers differently than the field of manual magnetic resonance sample changers. That is, those skilled in the art have considered the field of automatic sample changers to be a progressive improvement over the manual sample changer field, and therefore they do not necessarily look back upon this field to progress further. Likewise, because of the differing spin velocities, and sample preparation requirements of liquids and solids these two fields of NMR are also very different.
The availability of automatic liquid sample changers in magnetic resonance spectroscopy has been known by those skilled in the art for some time. Independent automatic insertion, analysis and removal of liquid samples has led to a number of U.S. and foreign patents over the years. However, prior to the present invention some basic problems remained which negatively affected the overall system reliability as well as posed some special analyses difficulties for the spectroscopist. These problems included, but were not limited to, the use of an affirmative means, such as compressed gas, to eject samples from the magnetic field after analysis and the time consuming task of fitting each and every sample tube with its own, often bulky, spinner.
Difficulties encountered when using a compressed gas for ejection were sometimes related to the inaccuracies of gas pressure control, resulting in too little or too much pressure. Others skilled in the art have noted that under such conditions samples could either fail to reach an exitable point or they could eject in a rather unpredictable manner from their analysis positions. U.S. Pat. No. 4,859,948 to Kuster utilizes an adjustable control valve to regulate the quantity of compressed gas used in ejecting the sample containers. This approach typifies that taken by those skilled in the art as one to compensate for a limitation rather than one which attempts to overcome the reason for the limitation.
Another difficulty occurred when a spinner served a dual purpose--acting as the sole support for the sample as well as the spinning mechanism, as in U.S. Pat. No. 3,796,946 to Utsumi. Positioned usually in the middle 3/4 of the sample tube, the spinner as a support offered little in the way of stabilization. Instead, the inherent wobble of a sample container would be accentuated at the distal ends of the container, with the greatest degree of wobble occurring at the heavier closed end located within the analysis area of the NMR spectrometer. This aspect has created the problem of undesirable spectral sidebands during the spinning of the sample in analysis. Because solid samples are spun at rates which are magnitudes greater than those of liquid samples, the problem of sample wobble in solid NMR was not analogous to the problem of sample wobble in liquid NMR. This is essentially one reason the two fields are so distinct from one another.
Another difficulty commonly accepted by those skilled in the art was the use of a single passage or opening for the insertion and removal of the samples. This significantly limited the speed with which samples could be changed because a sample would have to be removed completely before a subsequent sample could be inserted. In U.S. Pat. No. 4,581,583 to Van Vliet et al., the principal objective as stated was to increase the rate of changing samples. But even with this narrow focus Van Vliet failed to realize, among other things, the value of separate entrance and exit openings to enhance the potential speed with which samples could be analyzed.
An important commercial problem encountered in the prior art is one of an economic nature. That is, prior to the present invention other systems were so complex in design that their cost had been a significant deterrent to companies or other institutions which would have otherwise benefitted from such a system.
While at first glance some of these difficulties might seem easily resolved, it appears that in the general field of magnetic resonance spectroscopy a dichotomy exists between the theorists and the mechanical technicians. On the one hand, the theorists are devoted almost entirely to the advancement of their field through discovery based on theory-related principles. They spend little time on the mechanically-orientated aspects of magnetic resonance devices. On the other hand, the technicians, while often capable of designing mechanical accessories, were typically unaware of the specific problems that existed, making it difficult for them to either recognize the need for or to conceptualize the present invention.
The problems, as explained above, were dealt with in a number of ways by those skilled in the art. Some designs were put forth in which samples were inserted by a mechanical ram into a spinning air motor device located within the analysis area of the magnetic resonance spectrometer. This may have eliminated the use of individual spinners and ejection air but created other significant reliability problems. The use of mechanical parts to perform any function usually requires an increased amount of repair and replacement occurrences. To maintain reliability of mechanical systems there has always been the likelihood of increased cost.
Others concentrated on the spectral sideband problem, attempting to stabilize the sample during spinning by using a heavy spinner or a larger spinner for increased surface contact. This approach required an increase in the velocity of the spin and ejection air to overcome the higher coefficient of friction and lifting requirements of a heavier sample. This technique is the one employed by Utsumi. Large stabilizing blades are supplied to steady the sample in rotation as they also frictionally engage the sample tube holder to act as a support.
In order to solve these and other problems encountered in the field of automatic magnetic resonance sample changers, the present invention was developed. By supplying not one, but two separate openings the samples may be inserted into one and removed from the other. Furthermore, by linking these separate openings vertically the sample may be carried into the analysis area by gravity, and more importantly the sample may also exit the analysis area by gravity. The present invention has fewer mechanical parts to wear out or maintain and the present invention needs no failure-prone compressed air to eject the sample. To overcome the problems caused by the use of individual spinners the present invention has been designed to utilize a component essential to liquid state NMR analysis--the sample container cap--to efficiently spin the sample.
While the basis of the present invention could be considered to be relatively simple, it is a fact that those skilled in the art of automatic magnetic resonance sample changers failed to realize the proper combination and selection of elements to overcome a combination of prior limitations. Although the implementing arts and elements of the present invention were available, those in the field focusing on the problems of a proper automatic sample changer had not been able to solve these problems. The preconception that a single opening was a given, resulted in those skilled in the art teaching away from the direction of the present invention. While there had been substantial attempts by those skilled in the art at overcoming the problem of undesirable spectral sidebands in magnetic resonance spectroscopy, until the present invention such attempts had not resulted in an adequate economical solution to the problem.
Finally, the seeming presence of a dichotomy in skill levels in the field of NMR spectroscopy made solutions even more difficult. One group possessed an appreciation of the aforementioned problems but not the ability to successfully design a solution. The other group, while possessing the mechanical skill, was lacking a perception of the particular problems stated above and an appreciation that changes could be made in most systems without impacting their scientific capabilities. Just such a communication "gap" had caused designers to retain many restrictions even after the reason for the restrictions had gone. For instance, restrictions imposed by the use of electro-magnets in NMR spectrometers need not have been imposed once superconducting magnets were utilized. In these systems mechanical and/or electrical components and assemblies were typically located beneath the analysis area, requiring samples to be removed through the top. Now with the longer super-conducting magnets, chambers can lend themselves to separate entrance and exit openings.
As an instructive guide to show the direction taken by some persons skilled in the art and the focus of their inventions, the following information is submitted. It is not an intent to imply that each should be necessarily considered relevant to the disclosed invention, rather only to demonstrate the problems encountered in the general field of magnetic resonance sample changers and how differently they were dealt with compared to the approach of the present invention.
U.S. Pat. No. 3,796,946 to Utsumi, et al., relates to a sample intake means for inserting and removing a sample from a magnetic resonance spectrometer. It operates by lifting the cover to raise the sample tube holder, and then closing the cover to lower the holder into the analysis area. This is all done manually rather than automatically.
U.S. Pat. No. 4,088,944 to Engler, et al., discloses a turbine for centering the sample tube in the same rotational axis. The tube is frictionally engaged at two locations proximal to its lower end, thereby reducing the wobble of the tube.
U.S. Pat. No. 4,091,323 to Landis is an automated sample changer for NMR Spectroscopy. A robotic arm is maneuvered up, down, back and forth by pneumatic means controlled by a gas fluidics circuit. Samples are subsequently inserted into and removed from an upper opening in the spectrometer guide tube.
U.S. Pat. No. 4,581,583 to Van Vliet and Gordon is an automatic sample selecting and positioning apparatus which utilizes individual spinners, as well as ejection air. Samples are inserted and ejected through the same opening in the top of the spectrometer and replaced to their original position in a sample carousel.
European Patent Number 0197791 A2 issued to Smallcombe and Codrington pertains to an automated apparatus for presentation of samples to an NMR spectrometer. However, the focus seems to be the use of coding labels, and an optical detection channel for identifying samples before, during and after analysis. Each sample is subjected to the mechanical handling of a robotic arm which serves to grab the sample, place it in the spectrometer, then remove the sample and put it back in the rack.
U.S. Pat. No. 4,859,948 to Kuster relates to manual sample changers for use with large magnet arrangements. The sample carrier is lowered into and ejected from the upper opening of the guide tube via pressurized gas. One of its key features is that it requires little space to operate.
U.S. Pat. No. 4,859,949 to McKenna discloses an automatic sample changer which frictionally engages the sample container at two locations during analysis. Sample containers are inserted and removed from a single opening in the spectrometer guide tube.
While each of the aforementioned patents represents a significant invention in their respective fields, those related to magnetic resonance automatic liquid sample changers have not utilized the combination of key aspects of the present invention to accomplish their individual goals.